When considering a ratio of the proportion of the elderly people in Korea announced in National Statistics in October 2003, a population of more than 65 years of age in 2000 reached 7.2% of the total population. It is expected that this ratio exceeds 14% to enter into an aging society in 2019. As such, as the aging problem comes to as a social issue, the public interest on characteristics of the aging population and the welfare for the aged such as housing, health, culture, and leisure have been increased, thereby increasing the demand for statistics therefore. The core of this change is that chronic degenerative diseases comes to as a larger problem than all acute infectious diseases which have been the leading cause of the death over the past 50 years due to the increase of the aging population. Particularly, the death due to a cerebrovascular disease among the chronic degenerative diseases has been ranked as the second among death rates due to a single disease.
Dementia has an impairment in normal daily life in profession, social and personal relationships, and means that one or more among four kinds such as a speech impairment, disorientation, poor numeracy, and a change in personality and emotion in addition to a memory impairment. The dementia is a pathological symptom which needs to be distinguished from a normal aging, and classified into Alzheimer's dementia, vascular dementia, and other dementias caused by alcohol addiction, trauma, and a sequela of Parkinson's disease depending on a cause. The vascular dementia causes cerebral infarction, stroke, or the like, and it has been known that brain cells around a disease portion are damaged to cause symptoms in early such as memory loss. On the other hand, the Alzheimer's dementia is a degenerative brain disease caused by the destruction of brain cells, and has symptoms such as memory loss, a change in personality, and poor thinking and slowly progresses, but it has been known that most patients die due to pneumonia and the like within 8 to 10 years. According to recent epidemiological studies, it is reported that risk factors of a cerebrovascular disease such as high blood pressure, diabetes, hyperlipidemia, and heart diseases, cerebrovascular disease increases the incidence of not only vascular dementia but also Alzheimer's dementia, but the cause of a disease or a treating method is still unknown.
As a representative animal test model used for the dementia studies, a dementia mode of a white mouse induced by scopolamine acts as an antagonist to a muscarinic receptor to hinder coupling of acetylcholine and the receptor, and as a result, causes memory and cognitive impairments due to the reduction of a transfer amount of acetylcholine.
The Alzheimer's disease (AD) is characterized by loss of neurons, and a extracellular senile plaque consisting of amyloid β protein (amyloid-beta; Aβ) which is a 39-43 amino acid peptide derived from amyloid precursor protein as a major component. As the results of in vitro and in vivo studies, it is reported that the Aβ or a fragment of the Aβ peptide has a toxicity effect, and as a result, it is shown that the Aβ plays an important role in the incidence of the AD (Butterfield et al., Free Radical Biology and Medicine, 2002, 32:1050-1060; Butterfield et al., Free Radical Biology and Medicine, 2007, 43:658-677). During culture, the Aβ directly induces the death of the neurons, and makes the neurons to be vulnerable to excited toxicity and oxidative damage. An N-methyl-D-aspartate (NMDA) receptor acts as a medium of a selective substrate of Aβ coupling or Aβ-induced glutamate excited toxicity. The NMDA receptor is particularly a ligand-gate/voltage-sensitive cation channel which is highly permeable to Ca2+. A wide increase of [Ca2+]i directly leads to cell dysfunction, hysteria, or death. Accordingly, as verified by the report that a neurotoxic effect of the Aβ is reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) which is an antagonist of a non-competitive NMDA receptor, Ca2+ flow through the NMDA receptor by Aβ exposure plays a crucial role in the Aβ-induced neurotoxicity. It is believed that formation of reactive oxygen species (ROS) is also involved in the incidence of the degenerative brain diseases. Some evidence support involvement of oxidative stress as an active factor in an Aβ-mediated neuropathy, by triggering or facilitating neurodegeneratio by widespread molecular shapes hindering neuron homeostasis. However, the clinical benefit of the NMDA receptor antagonists and a direct blocker of the neuron channel are debatable because the NMDA receptor antagonists and the direct blocker have the lack of remarkable efficiency or serious side effects.
As normal subjects are getting older, the normal subjects suffer from some degree of memory impairment, but symptoms such as a change in personality which are specifically shown to Alzheimer's patients are not shown, which is called a mild cognitive impairment (MCI). The MCI is considered as a prodrome of Alzheimer's disease, and characterized by a short-term memory loss, a spatial memory loss, and emotional imbalance, and the prodrome is classified into stages. Among the prodromes, the MCI related with the memory loss is called an amnestic MCI, and probability that a 65-year-old normal person is converted to an Alzheimer patient within a certain period is 1 to 3%, whereas in a group with the amnestic MCI, eight out of ten people are converted to Alzheimer patients, and in the case of the amnestic MCI, it is considered that possibility to be developed to Alzheimer's dementia is high.
Parkinson's disease as a chronic progressive, degenerative disease of a nervous system that rest tremor, mortis, bradypragia, and postural instability characterfully appear shows a neuropathologic characteristic in which a nerve cell of dopamine distributed in substantia nigra of a brain (substantia nigra pars compacta, SNc) is gradually lost (Calne et al., 1983, Heikkila 1984). A parkinsonian patient is estimated as approximately 1% of population in approximately 60 ages or more. A cause of the Parkinson's disease is not definitely established, but ‘multifactorial hypothesis’ that a genetic factor and an environmental factor interact with each other is most commonly accepted. The Parkinson's disease occurs for most of parkinsonian patients without a family history, but approximately 10% appear as a familial Parkinson's disease.
As a symptomatic therapy agent for increasing the reduced amount of dopamine of the Parkinson's disease, L-Dopa is generally used at present. After L-Dopa is used, L-Dopa makes a progress of the Parkinson's disease slow and shows reduction of clinical symptoms, but when L-Dopa is taken for a long time, a side effect such as an involuntary movement, vomiting, or the like is caused (Clarke and Deane, 2001). Besides, medicines used to therapy the Parkinson's disease include Dopamine Agonists, catechol-O-methyltransferase inhibitor (COMT inhibitor), monoamine oxidase B (MAO-B inhibitors), Anti-cholinergics, and the like. An animal model used to research the Parkinson's disease is an animal model using 6-hydroxydopamine (6-OHDA), rotenone, or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Among them, it was first known that MPTP causes the Parkinson's disease for human by drug addicts in 1982 and this shows the clinical symptoms clinically similar in primates and mouse as well as people, and as a result, the MPTP is evaluated as an appropriate experimental animal model to research a condition physiology change of the Parkinson's disease. Mechanisms of injury of the dopamine nerve cell by the MPTP has not yet definitely appeared, but in recent years, it has been reported that inflammation increases in cerebrums by MPTP exposure and the inflammation is an important process for a physiology research of the Parkinson's disease. Since the MPTP causes acute degeneration of a nigrostriatal pathway in the mouse and monkey, the MPTP has been used as a useful Parkinson model. Further, it has been known that the animal experiment model by the MPTP as an acute inflammation step of the Parkinson's disease is suitable for researching a therapy technology of function damage of mitochondria and cell death by oxidative stress or a neuroprotection effect of drug.
Epilepsy as a chronic disease group due to repeated occurrence of an epilepsy seizure even though there is no cause factor which may cause a single epilepsy seizure, that is, physical abnormality accompanies neurobiological, mental, cognitive, and social changes (Robert et al., 2005). Attack rate and prevalence rate of the epilepsy show a U shape in which the attack rate and the prevalence rate are highest and thereafter, abruptly decrease within 1 year after birth and abruptly increases in an old generation of 60 ages or more, and main causes include stroke, congenital deformity, head injury, encephalitis, a brain tumor, degenerative encephalopathy, inheritance, a premature baby, damage before and after childbirth, and the like.
As a representative animal experiment model used for researching the epilepsy, a white mouse epilepsy model induced by Kainic acid has neuroexcitotoxicity and an epilepsy seizure through a Kainic acid receptor and accompanies cognitive impairment and damage of the nerve cell.
Houttuynia cordata (THUNB.) as turning of Houttuynia cordata (THUNB.) which is a plant of Saururaceae inhibits in a southeast area of Asia, particularly, Japan, Korea, and the like. The Houttuynia cordata is also called ten medicines because of ten medicinal effects and it is derived that a stem is similar as a sweet potato leaf and when a fresh leaf is touched, a smell of fish stunk up to be called Houttuynia cordata. Houttuynia cordata may be used medicinally or edibly and is classified as animals and plants of which only a minimum amount may be used as supplementary material in food code and food raw material classification and it has been widely known that Houttuynia cordata has cardiac, diuretic, antibiotic, detoxification, and anticancer effects pharmacologically, and Houttuynia cordata is used as cosmetics and health functional food that assist detoxification and beauty privately.
It is reported that the Houttuynia cordata contains a lot of decanoyl acetaldehyde compounds that have antibiotic, antivirus, and fungal inhibition effects and flavonoid-series compounds that show diuretic, cardiac, and evacuation effects. In particular, it is written in a Botanical List that the Houttuynia cordata removes a boil, poison, and the like in addition to a fever alleviation action, and it is written in Jungyang dictionary that the Houttuynia cordata clean blood, removes inflammation, and helps urine drainage. Meanwhile, Houttuynia cordata as a medicinal plant used in herbal and private remedies and in Korean Patent Registration No. 521813 as the related art using the medicinal plant discloses a pharmaceutical composition containing a mixed crude medicine such as a soybean, ganoderma, Houttuynia cordata, feeding mugwort, licorice, and the like as an effective component is less and safe in a side effect and toxicity, and is used for anticancer therapy, reinforcement of immunization, and therapy of artery hardening, and a manufacturing method thereof.
Ampelopsis japonica Makino as an obese tuberous root of ampelopsis japonica has a shape in which both ends are sharpened in a long oval shape or a pyramidal shape. Since the taste is bitter and a property is cold, ampelopsis japonica Makino cools heat and release poison. Ampelopsis japonica Makino is used for taking medicine or external use, and carbunculosis, and the like, are controlled and new skin is granulated, and when leprosy or abscess is not treated by a blue heat action or new skin is treated by granulating new skin when damage is applied with water or fire.
Accordingly, while the inventors effort the development of a natural substance having treating and prevention effects for dementia, Parkinson's disease, or epilepsy, the inventors confirm that an extract of Houttuynia cordata or a mixture of an extract of Houttuynia cordata and an extract of Ampelopsis japonica Makino has a cognition improved effect in an Amyloid-β (Abeta) oligomer toxicity induced model of a white mouse, a cell protection effect for Amyloid-β induced toxicity in cortical and hippocampal cells, a cell protection effect for a 6-hydroxydopamine (6-OHDA) induced toxicity in an SH-SY5Y cell and a PC12 cell, and a cognition improved effect and a cell protection effect in a Kainic acid toxicity induced model of a white mouse to find that the extract of Houttuynia cordata or the mixture of the extract of Houttuynia cordata and the extract of Ampelopsis japonica Makino may be effectively used for preventing and treating dementia, Parkinson's disease, or epilepsy, thereby completing the present invention.